The synthesis of sorbinil, by optical resolution of RS-2,3-dihydrospiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'-dione (the racemic compound corresponding to sorbinil) or of precursor 6-fluoro-4-ureidochroman-4-carboxylic acid affords at least equal yields of the undesired enantiomer of sorbinil or of its precursor (either one usually contaminated with the corresponding racemate). The overall efficiency of the process is greatly enhanced by conversion of these by-products back to sorbinil intermediate, 6-fluoro-4-chromanone, which is then recycled to sorbinil. Not only is the overall yield of sorbinil greatly increased, but disposal problems associated with these by-products (necessarily formed in yields at least equivalent to sorbinil or its precursor) are avoided.
The present invention is applicable not only in the original synthesis of sorbinil, involving optical resolution of racemate with brucine (Sarges, U.S. Pat. No. 4,130,714), but also to more recently discovered processes: Sysko, U.S. patent application Ser. No. 440,686 for "Sorbinil by Optical Resolution with Aminopinane Derivatives"; and Cue and Moore, U.S. patent application Ser. No. 440,641, by "Sorbinil for Optical Resolution of Precursor 6-Fluoro-4-Ureidochroman-4-Carboxylic Acid"; both filed concurrently with the present application).